Monomethyl Fumarate Challenges Multiple Sclerosis

Multiple sclerosis is a neurodegenerative disease in which the protective covering of nerves are eaten away by the immune system. However, a novel bioequivalent of dimethyl fumarate (Tecfidera) may soon be offering another treatment option for patients.

In November 2018, the US Food and Drug Administration (FDA) has granted tentative approval to Banner Life Sciences for its new drug application (NDA) for monomethyl fumarate (Bafiertam) delayed-release 95mg capsules, for the treatment of relapsing forms of multiple sclerosis. Monomethyl fumarate is a novel bioequivalent of dimethyl fumarate (Tecfidera). According to the FDA, monomethyl fumarate met the required safety, efficacy, quality, and bioequivalence standards for approval.

Biogen, maker of Tecfidera, dismissed its lawsuit against Banner in September 2018, in which Biogen claimed that monomethyl fumarate would infringe on patents 7,320,999 and 8,399,514 related to Tecfidera. The FDA’s final approval of monomethyl fumarate is expected once Biogen’s current patent no. 7,619,001 for dimethyl fumarate expires on June 20, 2020.

“We are very pleased with the FDA’s tentative approval and this important milestone brings us one step closer to providing another treatment option to patients living with relapsing-remitting multiple sclerosis,” Franck Rousseau, MD, CEO of Banner Life Sciences LLC, said in a statement. “In anticipation of final approval, we will establish our commercial vehicle, continue developing the clinical profile of monomethyl fumarate and refine our strategic positioning for this important drug.”

Monomethyl fumarate is a compound that can cross the blood-brain barrier. The precise mechanism of action has not yet been fully elucidated, but it is presumed to activate transcription factor known as the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway.

Tecfidera, the prodrug of monomethyl fumarate, is quickly converted from dimethyl fumarate into monomethyl fumarate in the body. Dimethyl fumarate has been shown in 2 separate studies to reduce the risk of relapse by 49% and 34%, and to reduce the number of relapses by 53% and 44%, compared to placebo.

The immunomodulatory properties of dimethyl fumarate have been demonstrated to alter the profile of the immune system by reducing the number of blood lymphocytes (particularly the pro-inflammatory subsets), and to block pro-inflammatory cytokine production.

“It’s similar but not completely the same as Tecfidera—it’s the same metabolite,” Douglas MacDougall, managing partner for MacDougall Biomedical Communications told MD Magazine®. “Monomethyl fumarate will compete with dimethyl fumarate as well as the other drugs that are currently FDA-approved for relapsing MS.

The news of the FDA’s tentative approval for Banner Life Sciences’ NDA positions monomethyl fumarate to enter the market before any generic versions of dimethyl fumarate could be eligible to follow suit. At this time, nearly 30 companies have filed abbreviated NDAs to produce generic versions of Tecfidera, according to Rousseau, but none could bring them to the market sooner than September 2020.

MacDougall anticipates the launch of monomethyl fumarate on the market of available options for DMTs for RMS by early September 2020.

“We still have quite a bit of time to work out the positioning in the market. It could be July or it could be August, but most likely will be early September,” said MacDougall.

A key feature offered by monomethyl fumarate is its lower dose when compared to dimethyl fumarate. Whether a lower dose of a different application of this class of drug will result in fewer side effects is yet to be explored in a clinical trial.